By Yue Zhang, MD, MPH
While colorectal cancer (CRC) remains a common and lethal disease, mortality rates have declined in recent years. Patients live much longer with a better quality of life due to improved screening and treatments.
A concerning observation, however, is the increasing rate of diagnosis in younger patients. This led to a recent update of CRC screening recommendations to begin at age 45 instead of age 50 for anyone at average risk and sooner with a family history of the disease or other known risk factors.
Thankfully, ongoing advances in immunotherapy have significantly extended survival in certain metastatic CRC patients.
Perhaps the best example is the Phase III KEYNOTE-177 study, a Phase III trial that compared the efficacy of frontline immunotherapy with chemotherapy in Stage IV patients with microsatellite-high (MSI-H) or mismatch repair deficient (dMMR) metastatic CRC.
ASCO 2020 reported that pembrolizumab doubled progression-free survival versus standard of care chemotherapy, with less cytotoxicity and fewer severe treatment-related side effects. ESMO 2020 also released data confirming an improved quality of life with immunotherapy.
Pembrolizumab obtained FDA approval immediately and is now the preferred frontline treatment for MSI-H/dMMR metastatic CRC. The follow-up KEYNOTE 164 reported 31.4 months of median overall survival for pembrolizumab in refractory MSI-H/dMMR metastatic CRC.
Another exciting immunotherapy combination of Nivolumab/Ipililumab demonstrated a dramatic response rate of 60 percent for frontline treatment of MSI-H/dMMR metastatic CRC.
A growing number of other promising targeted therapies have the potential to transform clinical practice. In 2020, the FDA approved a combination cocktail of encorafenib and cetuximab for refractory CRC patients with a BRAF V600E mutation.
The BEACON CRC trial demonstrated that the combination showed significant improvements in overall survival, response rate and progression-free survival in these patients with historically dismal outcomes.
Another medication, sotorasib, is designed to bind to a G12C mutated KRAS protein and “turn off” signals that fuel tumor growth. This is the first breakthrough after a prolonged search for the “undruggable” driver mutation of KRAS.
The DESTINY-CRC01 study also showed exciting results with a 45 percent response rate in HER2-positive refractory CRC patients. Another interesting agent, tucatinib, is under evaluation for HER2 positive CRC patients.
Newer therapeutic approaches should expand further in the near future, with multiple clinical trials ongoing.
As oncologists in these exciting times, we should build better treatment plans using a multidisciplinary approach, next generation sequencing of tumor tissue for MMR status and other potential treatable mutations, and genetic evaluation for certain patients.
All physicians can help patients by emphasizing regular screenings with colonoscopy to catch the disease as early as possible. Education on lifestyle choices and/or changes for cancer prevention is also important, including exercising regularly, avoiding high-fat and processed foods, losing weight if necessary, limiting alcoholic beverages, and not smoking.
Even if a patient already has advanced metastatic disease at diagnosis, they may still have effective treatment options. Their futures – and ours as their providers – should only grow brighter with time.
Dr. Zhang is a medical oncologist and hematologist with Virginia Oncology Associates, specializing in gastrointestinal and renal cancers. She practices in Norfolk and Virginia Beach. virginiacancer.com
